{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:58:37Z","timestamp":1792681117572,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Prior sepsis studies evaluating antibiotic timing have shown mixed results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4\u20133.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05\u20131.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour\u2019s delay in antibiotic administration was 0.3% (95% CI, 0.01\u20130.6%; P\u2009=\u20090.04) for sepsis, 0.4% (95% CI, 0.1\u20130.8%; P\u2009=\u20090.02) for severe sepsis, and 1.8% (95% CI, 0.8\u20133.0%; P\u2009=\u20090.001) for shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201609-1848oc","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T12:03:55Z","timestamp":1490616235000},"page":"856-863","source":"Crossref","is-referenced-by-count":898,"title":["The Timing of Early Antibiotics and Hospital Mortality in Sepsis"],"prefix":"10.1093","volume":"196","author":[{"given":"Vincent X.","family":"Liu","sequence":"first","affiliation":[{"name":"Kaiser Permanente Division of Research, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Fielding-Singh","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Greene","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Division of Research, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Baker","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Division of Research, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore J.","family":"Iwashyna","sequence":"additional","affiliation":[{"name":"Center for Clinical Management Research, VA Ann Arbor Health System, Ann Arbor, Michigan"},{"name":"Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Primary Care and Outcomes Research, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel J.","family":"Escobar","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Division of Research, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,10,1]]},"reference":[{"key":"2026032023464590100_bib1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1097\/CCM.0b013e31827e83af","article-title":"Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012","volume":"41","author":"Dellinger","year":"2013","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(15)70112-X","article-title":"Sepsis: a roadmap for future research","volume":"15","author":"Cohen","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"2026032023464590100_bib3","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1001\/jama.2015.7885","article-title":"Septic shock: advances in diagnosis and treatment","volume":"314","author":"Seymour","year":"2015","journal-title":"JAMA"},{"key":"2026032023464590100_bib4","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N Engl J Med"},{"key":"2026032023464590100_bib5","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1186\/s13054-014-0533-x","article-title":"Prehospital intravenous access and fluid resuscitation in severe sepsis: an observational cohort study","volume":"18","author":"Seymour","year":"2014","journal-title":"Crit Care"},{"key":"2026032023464590100_bib6","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1164\/rccm.201204-0713OC","article-title":"Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome","volume":"186","author":"Seymour","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023464590100_bib7","author":"Nanayakkara"},{"key":"2026032023464590100_bib8","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1056\/NEJMp1400276","article-title":"Regulatory mandates for sepsis care: reasons for caution","volume":"370","author":"Rhee","year":"2014","journal-title":"N Engl J Med"},{"key":"2026032023464590100_bib9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.7326\/0003-4819-149-1-200807010-00007","article-title":"Public reporting of antibiotic timing in patients with pneumonia: lessons from a flawed performance measure","volume":"149","author":"Wachter","year":"2008","journal-title":"Ann Intern Med"},{"key":"2026032023464590100_bib10","author":"National Action Plan for Combating Antibiotic-Resistant Bacteria"},{"key":"2026032023464590100_bib11","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1128\/MMBR.00016-10","article-title":"Origins and evolution of antibiotic resistance","volume":"74","author":"Davies","year":"2010","journal-title":"Microbiol Mol Biol Rev"},{"key":"2026032023464590100_bib12","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1001\/jama.289.7.885","article-title":"Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use","volume":"289","author":"Neuhauser","year":"2003","journal-title":"JAMA"},{"key":"2026032023464590100_bib13","first-page":"545","article-title":"Emergency department operational changes in response to pay-for-performance and antibiotic timing in pneumonia","volume":"14","author":"Pines","year":"2007","journal-title":"Acad Emerg Med"},{"key":"2026032023464590100_bib14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jen.2014.12.007","article-title":"Impact of nurse-initiated ED sepsis protocol on compliance with sepsis bundles, time to initial antibiotic administration, and in-hospital mortality","volume":"41","author":"Bruce","year":"2015","journal-title":"J Emerg Nurs"},{"key":"2026032023464590100_bib15","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1097\/CCM.0000000000001142","article-title":"The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis","volume":"43","author":"Sterling","year":"2015","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/1742-6723.12394","article-title":"INITIAT-E.D.: Impact of timing of INITIation of Antibiotic Therapy on mortality of patients presenting to an Emergency Department with sepsis","volume":"27","author":"Wisdom","year":"2015","journal-title":"Emerg Med Australas"},{"key":"2026032023464590100_bib17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/MAJ.0000000000000423","article-title":"Prognostic value of timing of antibiotic administration in patients with septic shock treated with early quantitative resuscitation","volume":"349","author":"Ryoo","year":"2015","journal-title":"Am J Med Sci"},{"key":"2026032023464590100_bib18","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1097\/CCM.0b013e3181cc4824","article-title":"Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department","volume":"38","author":"Gaieski","year":"2010","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib19","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1097\/01.CCM.0000217961.75225.E9","article-title":"Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock","volume":"34","author":"Kumar","year":"2006","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib20","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1097\/CCM.0000000000000330","article-title":"Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program","volume":"42","author":"Ferrer","year":"2014","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib21","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1164\/rccm.200812-1912OC","article-title":"Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study","volume":"180","author":"Ferrer","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023464590100_bib22","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1007\/s00134-003-1957-y","article-title":"Improved survival of critically ill cancer patients with septic shock","volume":"29","author":"Larch\u00e9","year":"2003","journal-title":"Intensive Care Med"},{"key":"2026032023464590100_bib23","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1001\/jama.1997.03550230056037","article-title":"Quality of care, process, and outcomes in elderly patients with pneumonia","volume":"278","author":"Meehan","year":"1997","journal-title":"JAMA"},{"key":"2026032023464590100_bib24","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/archinte.164.6.637","article-title":"Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia","volume":"164","author":"Houck","year":"2004","journal-title":"Arch Intern Med"},{"key":"2026032023464590100_bib25","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1378\/chest.122.1.262","article-title":"Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia","volume":"122","author":"Iregui","year":"2002","journal-title":"Chest"},{"key":"2026032023464590100_bib26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/CCM.0000000000000723","article-title":"Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study","volume":"43","author":"Levy","year":"2015","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib27","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/apt.13135","article-title":"Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study","volume":"41","author":"Karvellas","year":"2015","journal-title":"Aliment Pharmacol Ther"},{"key":"2026032023464590100_bib28","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1097\/CCM.0b013e31821e87ab","article-title":"Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol","volume":"39","author":"Puskarich","year":"2011","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib29","doi-asserted-by":"crossref","first-page":"R42","DOI":"10.1186\/cc13755","article-title":"Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study","volume":"18","author":"Bloos","year":"2014","journal-title":"Crit Care"},{"key":"2026032023464590100_bib30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13054-015-0936-3","article-title":"The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study","volume":"19","author":"de Groot","year":"2015","journal-title":"Crit Care"},{"key":"2026032023464590100_bib31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ajem.2013.09.008","article-title":"Timing and appropriateness of initial antibiotic therapy in newly presenting septic patients","volume":"32","author":"Vilella","year":"2014","journal-title":"Am J Emerg Med"},{"key":"2026032023464590100_bib32","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1097\/CCM.0000000000001013","article-title":"Impact of sepsis classification and multidrug-resistance status on outcome among patients treated with appropriate therapy","volume":"43","author":"Burnham","year":"2015","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib33","first-page":"A2741","article-title":"The timing of early antibiotics and hospital mortality in sepsis [abstract]","volume":"193","author":"Fielding-Singh","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023464590100_bib34","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1097\/01.CCM.0000050454.01978.3B","article-title":"2001 SCCM\/ESICM\/ACCP\/ATS\/SIS International Sepsis Definitions Conference","volume":"31","author":"Levy","year":"2003","journal-title":"Crit Care Med"},{"key":"2026032023464590100_bib35","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/jama.2014.5804","article-title":"Hospital deaths in patients with sepsis from 2 independent cohorts","volume":"312","author":"Liu","year":"2014","journal-title":"JAMA"},{"key":"2026032023464590100_bib36","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1513\/AnnalsATS.201304-099OC","article-title":"Fluid volume, lactate values, and mortality in sepsis patients with intermediate lactate values","volume":"10","author":"Liu","year":"2013","journal-title":"Ann Am Thorac Soc"},{"key":"2026032023464590100_bib37","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1164\/rccm.201507-1489OC","article-title":"Multicenter implementation of a treatment bundle for sepsis patients with intermediate lactate values","volume":"193","author":"Liu","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032023464590100_bib38","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/jhm.1929","article-title":"Early detection of impending physiologic deterioration among patients who are not in intensive care: development of predictive models using data from an automated electronic medical record","volume":"7","author":"Escobar","year":"2012","journal-title":"J Hosp Med"},{"key":"2026032023464590100_bib39","first-page":"158","article-title":"Risk adjusting community-acquired pneumonia hospital outcomes using automated databases","volume":"14","author":"Escobar","year":"2008","journal-title":"Am J Manag Care"},{"key":"2026032023464590100_bib40","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/MLR.0b013e3181589bb6","article-title":"Risk-adjusting hospital inpatient mortality using automated inpatient, outpatient, and laboratory databases","volume":"46","author":"Escobar","year":"2008","journal-title":"Med Care"},{"key":"2026032023464590100_bib41","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/MLR.0b013e3182881c8e","article-title":"Risk-adjusting hospital mortality using a comprehensive electronic record in an integrated health care delivery system","volume":"51","author":"Escobar","year":"2013","journal-title":"Med Care"},{"key":"2026032023464590100_bib42","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/jgs.14048","article-title":"The natural history of changes in preferences for life-sustaining treatments and implications for inpatient mortality in younger and older hospitalized adults","volume":"64","author":"Kim","year":"2016","journal-title":"J Am Geriatr Soc"},{"key":"2026032023464590100_bib43","doi-asserted-by":"crossref","first-page":"e104475","DOI":"10.1371\/journal.pone.0104475","article-title":"Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock--a quality improvement study","volume":"9","author":"Yokota","year":"2014","journal-title":"PLoS One"},{"key":"2026032023464590100_bib44","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1007\/s00134-015-3822-1","article-title":"A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators","volume":"41","author":"Angus","year":"2015","journal-title":"Intensive Care Med"},{"key":"2026032023464590100_bib45","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1056\/NEJMoa1404380","article-title":"Goal-directed resuscitation for patients with early septic shock","volume":"371","author":"Peake","year":"2014","journal-title":"N Engl J Med"},{"key":"2026032023464590100_bib46","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1056\/NEJMoa1401602","article-title":"A randomized trial of protocol-based care for early septic shock","volume":"370","author":"Yealy","year":"2014","journal-title":"N Engl J Med"},{"key":"2026032023464590100_bib47","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJMoa1500896","article-title":"Trial of early, goal-directed resuscitation for septic shock","volume":"372","author":"Mouncey","year":"2015","journal-title":"N Engl J Med"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/196\/7\/856\/67126124\/ajrccm_196_7_856.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/196\/7\/856\/67126124\/ajrccm_196_7_856.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:47:34Z","timestamp":1774064854000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/196\/7\/856\/8499134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,1]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,10,1]]},"published-print":{"date-parts":[[2017,10,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201609-1848oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,10]]},"published":{"date-parts":[[2017,10,1]]}}}